RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers

Irshad, Sheeba and Flores-Borja, Fabian and Lawler, Katherine and Monypenny, James and Evans, Rachel and Male, Victoria and Gordon, Peter and Cheung, Anthony and Gazinska, Patrycja and Noor, Farzana and Wong, Felix and Grigoriadis, Anita and Fruhwirth, Gilbert O. and Barber, Paul R. and Woodman, Natalie and Martin, Stewart G. (2017) RORγt+ innate lymphoid cells promote lymph node metastasis of breast cancers. Cancer Research, 77 (5). pp. 1083-1096. ISSN 1538-7445

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Abstract

Cancer cells tend to metastasize first to tumor-draining lymph nodes, but the mechanisms mediating cancer cell invasion into the lymphatic vasculature remain little understood. Here, we show that in the human breast tumor microenvironment (TME), the presence of increased numbers of RORγt+ group 3 innate lymphoid cells (ILC3) correlates with an increased likelihood of lymph node metastasis. In a preclinical mouse model of breast cancer, CCL21-mediated recruitment of ILC3 to tumors stimulated the production of the CXCL13 by TME stromal cells, which in turn promoted ILC3–stromal interactions and production of the cancer cell motile factor RANKL. Depleting ILC3 or neutralizing CCL21, CXCL13, or RANKL was sufficient to decrease lymph node metastasis. Our findings establish a role for RORγt+ILC3 in promoting lymphatic metastasis by modulating the local chemokine milieu of cancer cells in the TME.

Item Type: Article
Additional Information: 33 authors in total.
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Cancer and Stem Cells
Identification Number: 10.1158/0008-5472.CAN-16-0598
Depositing User: Martin, Stewart
Date Deposited: 24 May 2017 10:09
Last Modified: 21 Sep 2017 17:10
URI: http://eprints.nottingham.ac.uk/id/eprint/43055

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